TGF-β-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion

Journal of Cell Science
Samy LamouilleRik Derynck

Abstract

In cancer progression, carcinoma cells gain invasive behavior through a loss of epithelial characteristics and acquisition of mesenchymal properties, a process that can lead to epithelial-mesenchymal transition (EMT). TGF-β is a potent inducer of EMT, and increased TGF-β signaling in cancer cells is thought to drive cancer-associated EMT. Here, we examine the physiological requirement for mTOR complex 2 (mTORC2) in cells undergoing EMT. TGF-β rapidly induces mTORC2 kinase activity in cells undergoing EMT, and controls epithelial cell progression through EMT. By regulating EMT-associated cytoskeletal changes and gene expression, mTORC2 is required for cell migration and invasion. Furthermore, inactivation of mTORC2 prevents cancer cell dissemination in vivo. Our results suggest that the mTORC2 pathway is an essential downstream branch of TGF-β signaling, and represents a responsive target to inhibit EMT and prevent cancer cell invasion and metastasis.

References

May 28, 2013·Cancer Metastasis Reviews·Asfar S AzmiFazlul H Sarkar
Jun 30, 2012·Nature Cell Biology·Kamna Aggarwal, Joan Massagué
Aug 25, 2012·Nature Reviews. Cancer·Karen Block, Yves Gorin
Dec 1, 2012·Current Opinion in Oncology·Yoko KatsunoRik Derynck
Aug 8, 2013·Molecular Medicine·Tonyia Eaves-PylesIgor C Almeida
Feb 7, 2014·Journal of Biosciences·Mohammed Khursheed, Murali Dharan Bashyam
Jun 4, 2014·Mediators of Inflammation·Joanna Magdalena Zarzynska
Sep 25, 2014·Science Signaling·David M Gonzalez, Damian Medici
May 31, 2014·Journal of Shoulder and Elbow Surgery·Xuhui LiuBrian T Feeley
Jan 29, 2016·Journal of Clinical Medicine·Yanyuan WuJaydutt V Vadgama
Jan 1, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Banu IskenderHalit Canatan
Jun 6, 2015·Archives of Pathology & Laboratory Medicine·Lizandra JimenezJeffrey E Segall
Jul 22, 2014·Molecular Carcinogenesis·XianGuo ChenChaoZhao Liang
Feb 25, 2014·Biochimica Et Biophysica Acta·Aristidis Moustakas, Paraskevi Heldin
Dec 9, 2014·Cell Adhesion & Migration·E-Jean TanAristidis Moustakas
Sep 16, 2015·BMC Gastroenterology·Valentina MasolaUmberto Tedeschi
May 15, 2015·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Michael R DaviesBrian T Feeley
Feb 15, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Danysh AbetovDenis Bulanin
Dec 4, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiang XiaZhengjun Qiu
Dec 25, 2012·Cancer Treatment Reviews·Qiong WuZhiwei Wang
Sep 11, 2012·Biochimica Et Biophysica Acta·Masayo Sakaki-YumotoRik Derynck
Sep 23, 2014·Current Opinion in Cell Biology·Rik DerynckKoy Y Saeteurn

Citations

Jun 18, 2003·Cell·Yigong Shi, Joan Massagué
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Philippe P RouxJohn Blenis
Oct 7, 2004·Nature Cell Biology·Estela JacintoMichael N Hall
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Aug 18, 2005·Journal of Cell Science·Aristidis Moustakas, Carl-Henrik Heldin
Aug 27, 2005·Oncogene·Jiri Zavadil, Erwin P Böttinger
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Xin-Hua Feng, Rik Derynck
Oct 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Roland KaunasShu Chien
Nov 18, 2005·Cytokine & Growth Factor Reviews·Brian Bierie, Harold L Moses
Dec 21, 2005·The Journal of Cell Biology·Hanna Y IrieJoan S Brugge
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Jean Paul Thiery, Jonathan P Sleeman
Jun 24, 2006·Nature Reviews. Cancer·Brian Bierie, Harold L Moses
Aug 22, 2006·Current Biology : CB·Maria A FriasDavid M Sabatini
Apr 19, 2007·Nature Reviews. Genetics·Don X Nguyen, Joan Massagué
Jul 25, 2008·Journal of Cell Science·Nicholas O Deakin, Christopher E Turner
Dec 4, 2008·Cell Research·David Padua, Joan Massagué
Jan 21, 2009·Cell Research·Jian XuRik Derynck
Jan 27, 2009·Cancer Metastasis Reviews·Mahmut Yilmaz, Gerhard Christofori
Apr 4, 2009·The American Journal of Pathology·Michael W Klymkowsky, Pierre Savagner
Jun 3, 2009·The Journal of Clinical Investigation·Michael Zeisberg, Eric G Neilson
Oct 9, 2009·Journal of Cell Science·Mathieu Laplante, David M Sabatini
Oct 15, 2009·Science Signaling·Dimitrios IliopoulosPhilip N Tsichlis
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto

Related Concepts

Biochemical Pathway
Transforming Growth Factor beta
TOR complex 2
Cell Motility
Cosuppression
Neoplasms
Cancer Progression
Protein kinase B gamma
Gene Expression
Epithelial to Mesenchymal Transition

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.